These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Arrhythmogenic effects of arsenic trioxide in patients with acute promyelocytic leukemia and an electrophysiological study in isolated guinea pig papillary muscles.
    Author: Yamazaki K, Terada H, Satoh H, Naito K, Takeshita A, Uehara A, Katoh H, Ohnishi K, Hayashi H.
    Journal: Circ J; 2006 Nov; 70(11):1407-14. PubMed ID: 17062962.
    Abstract:
    BACKGROUND: Arsenic trioxide (As(2)O (3)) is a new promising regimen for patients with a relapse of acute promyelocytic leukemia (APL), but causes life-threatening arrhythmias. This study aimed to investigate the incidence and mechanism of arrythmogenesis caused by As(2)O(3). METHODS AND RESULTS: Standard 12-lead ECGs were monitored throughout As(2)O(3) therapy in 20 APL patients. As(2)O (3) (0.15 mg/kg) significantly prolonged the corrected QT interval (QTc: 445+/-7 to 517+/-17 ms, means+/-SE, p<0.01), and also increased the QTc dispersion and transmural dispersion of repolarization. Non-sustained ventricular tachycardias and torsades de pointes occurred in 4 and 1 patients, respectively. The action potentials and isometric contraction were measured in guinea pig papillary muscles during As(2)O (3) perfusion (350 micromol/L). The action potential duration was prolonged (APD(90): 150+/-11 to 195+/-12 ms at 60 min, p<0.01, n=5) and perfusion of As(2)O(3) in a low K(+) solution with a low stimulation rate augmented the prolongation of APD, and provoked early after-depolarizations and triggered activities. The prolonged exposure to As(2)O(3) induced muscle contracture, aftercontractions, triggered activities and electromechanical alternans. Tetrodotoxin or butylated hydroxytoluene partially prevented the As(2)O(3)-induced prolongation of APD. CONCLUSIONS: The prolonged QTc and spatial heterogeneity are responsible for the As(2)O(3)-induced ventricular tachyarrhythmias. In addition to prolongation of the APD, cellular Ca(2+) overload and lipid peroxidation might contribute to the electrophysiological abnormalities caused by As(2)O(3).
    [Abstract] [Full Text] [Related] [New Search]